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The spindle assembly checkpoint (SAC) is a highly conserved monitoring system that ensures a fidelity of chromosome segregation during mitosis. Bub3, a mitotic Checkpoint Protein, is a member of the Bub protein family, and an important factor in the SAC. Abnormal expression of Bub3 results in mitotic defects, defective spindle gate function, chromosomal instability and the development of aneuploidy cells. Aneuploidy is a state of abnormal karyotype that has long been considered as a marker of tumorigenesis. Karyotypic heterogeneity in tumor cells, known as "chromosomal instability" (CIN), can be used to distinguish cancerous cells from their normal tissue counterpart. In this review, we summarize the expression and clinical significance of Bub3 in a variety of tumors and suggest that it has potential in the treatment of cancer.
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Proteínas de Ciclo Celular , Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose , Aneuploidia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Instabilidade Cromossômica , Humanos , Mitose , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Fuso Acromático/metabolismoRESUMO
BACKGROUND: Different methods of acetabular reconstruction with total hip arthroplasty (THA) for Crowe II and III of adult developmental dysplasia of the hip (DDH) acetabular bone defect have been implemented clinically. However, the biomechanical effect of different augmented materials for acetabular reconstruction in THA on shell stability has never been discussed. METHODS: In the present study, autologous bone graft (BG)and metal (Ti6Al4V) augment (MA) were simulated with several acetabular bone defect models of DDH in THA. The contact pressure and micromotion between the shell and host bone were measured for evaluating the shell stability using a finite element method. RESULTS: The peak contact stress between shell and host bone was higher in the MA situation (12.45 vs 8.71 MPa). And the load transfer path was different, for BG models, the high local contact stresses were found at the junction of bone graft and host bone while for MA models the concentrated contact stresses were at the surface of MA. The peak relative micromotion between shell and host bone was higher in the MA situation (12.61 vs 11.13 µm). However, the peak micromotion decreased in the contact interface of MA and cup compared to the BG models. CONCLUSIONS: The higher micromotion was found in MA models, however, enough for bone ingrowth, and direct stronger fixation was achieved in the MA-cup interface. Thus, we recommended the MA can be used as an option, even for Crowe III, however, the decision should be made from clinical follow-up results.
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Artroplastia de Quadril , Luxação do Quadril , Prótese de Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Adulto , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Análise de Elementos Finitos , Luxação do Quadril/cirurgia , HumanosRESUMO
Synovial macrophage polarization and inflammation are essential for osteoarthritis (OA) development, yet the molecular mechanisms and regulation responsible for the pathogenesis are still poorly understood. Here, we report that pseudolaric acid B (PAB) attenuated articular cartilage degeneration and synovitis during OA. PAB, a diterpene acid, specifically inhibited NF-κB signalling and reduced the production of pro-inflammatory cytokines, which further decreased M1 polarization and vessel formation. We further provide in vivo and in vitro evidences that PAB suppressed NF-κB signalling by stabilizing PPARγ. Using PPARγ antagonist could abolish anti-inflammatory effect of PAB and rescue the activation of NF-κB signalling during OA. Our findings identify a previously unrecognized role of PAB in the regulation of OA and provide mechanisms by which PAB regulates NF-κB signalling through PPARγ, which further suggest targeting synovial inflammation or inhibiting vessel formation at early stage could be an effective preventive strategy for OA.
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Diterpenos/farmacologia , Osteoartrite/tratamento farmacológico , PPAR gama/genética , Sinovite/tratamento farmacológico , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/crescimento & desenvolvimento , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/crescimento & desenvolvimento , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/parasitologia , Camundongos , NF-kappa B/genética , Osteoartrite/genética , Osteoartrite/patologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Sinovite/genética , Sinovite/patologia , Fator de Transcrição RelA/genéticaRESUMO
Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Transcrição Gênica , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Proliferação de Células , Autorrenovação Celular , Progressão da Doença , Glioblastoma/diagnóstico , Humanos , PrognósticoRESUMO
BACKGROUND: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method. METHODS: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated. RESULTS: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %. CONCLUSIONS: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.
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Lesões do Manguito Rotador , Adulto , Artroscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Tendões , Resultado do TratamentoRESUMO
BACKGROUND: Total hip arthroplasty (THA) has been highlighted as the best treatment option for ankylosing spondylitis (AS) patients with advanced hip involvement. The huge blood loss associated with THA is a common concern of postoperative complications. Disease activity is a specific reflection of systematic inflammation of AS. The purpose of this study was to determine the effect of disease activity on blood loss during THA in patients with AS. METHODS: Forty-nine patients with AS who underwent unilateral THAs were retrospectively studied. Ankylosing Spondylitis Disease Activity Score (ASDAS) was employed to evaluate the disease activity. Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) formula was used to assess the surgical blood loss. The patients were divided into active group (ASDAS≥1.3; n = 32) and stable groups (ASDAS< 1.3; n = 17) based on the ASDAS. Peri-operative laboratory values, plain radiographs, intra-operative data, transfusion volume, and use of hemostatic agents were recorded and statistically analyzed. RESULTS: The ASDAS, pre-operative C-reactive protein level, erythrocyte sedimentation rate, and fibrinogen concentration in the active group were higher than the stable group (all P < 0.05); however, the pre-operative hemoglobin concentration and albumin level were higher in the stable group (both P < 0.05). The total blood loss during THA in stable patients was 1415.31 mL and 2035.04 mL in active patients (P = 0.006). The difference between the two groups was shown to be consistent after excluding the gender difference (P = 0.030). A high transfusion rate existed in both groups (stable group, 76.47% with an average of 1.53 units; active group, 84.37% with an average of 2.31 units), but there was no significant difference between the two groups (both P > 0.05). Compensated blood loss, corresponding to transfusion, was noted significantly more in the active group compared to the stable group (P = 0.027). There was no significant difference with regard to functional recovery (P > 0.05). CONCLUSION: Active AS patients are at high risk for increased blood loss during THA compared to stable patients. The underlying mechanism includes disorders of the coagulation and fibrinolytic systems, poor nutrition status, osteoporosis, imbalance of oxidative-antioxidative status and local inflammatory reaction. It is strongly recommended to perform THA in AS patients with stable disease.
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Artroplastia de Quadril/efeitos adversos , Perda Sanguínea Cirúrgica , Espondilite Anquilosante/complicações , Adulto , Sedimentação Sanguínea , Transfusão de Sangue , Feminino , Hemostáticos/uso terapêutico , Articulação do Quadril/cirurgia , Humanos , Masculino , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Numerous biomechanical and clinical studies comparing different techniques for rotator cuff repair have been reported, yet universal consensus regarding the superior technique has not achieved. A medially-based single-row with triple-loaded suture anchor (also referred to as the Southern California Orthopedic Institute [SCOI] row) and a suture-bridge double-row (SB-DR) with Push-Locks have been shown to result in comparable improvement in treating rotator cuff tear, yet the biomechanical difference is unknown. The purpose of the current study was to determine whether a SCOI row repair had comparable initial biomechanical properties to a SB-DR repair. METHODS: Six matched pairs of fresh-frozen cadaveric shoulders with full-thickness supraspinatus tendon tears we created were included. Two different repairs were performed for each pair (SCOI row and SB-DR methods). Specimens were mounted on a material testing machine to undergo cyclic loading, which was cycled from 10 to 100 N at 1 Hz for 500 cycles. Construct gap formation was recorded at an interval of 50 cycles. Samples were then loaded to failure and modes of failure were recorded. Repeated-measures analysis of variance and pair-t test were used for statistical analyses. RESULTS: The construct gap formation did not differ between SCOI row and SB-DR repairs (P = 0.056). The last gap displacement was 1.93 ± 0.37 mm for SCOI row repair, and 1.49 ± 0.55 mm for SB-DR repair. The tensile load for 5 mm of elongation and ultimate failure were higher for SCOI row repair compared to SB-DR repair (P = 0.011 and 0.028, respectively). The ultimate failure load was 326.34 ± 11.52 N in the SCOI row group, and 299.82 ± 27.27 N in the SB-DR group. Rotator cuff repair with the SCOI row method failed primarily at the suture- tendon interface, whereas pullout of the lateral row anchors was the primary mechanism of failure for repair with the SB-DR method. CONCLUSION: Rotator cuff repair with the SCOI row method has superior biomechanical properties when compared with the SB-DR method. Therefore, SCOI row repair using a medially-based single-row technique with triple-loaded suture anchor is recommended to improve the initial strength in treating full-thickness rotator cuff tears.
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Lesões do Manguito Rotador , Manguito Rotador , Fenômenos Biomecânicos , Cadáver , Humanos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Âncoras de Sutura , Técnicas de Sutura , SuturasRESUMO
Pikeperch (Sander lucioperca) is an economically important cool-water fish. In recent years, its cultivation has become threatened by higher temperatures in summer. We previously investigated the effects of heat stress on pikeperch liver under different temperatures, but the molecular mechanism of the heat-stress response is still unknown. This study applied consistent heat stress (29⯰C, 0-48â¯h) to pikeperch juveniles, and a transcriptomic profile of pikeperch liver under heat stress (29⯰C, 0â¯h) was performed by RNA-Seq. The antioxidant status, changes in liver histology, and antioxidant gene expression at different time points were examined. We identified 403 differentially expressed genes (DEGs), many of which were enriched in KEGG pathways, including protein processing in endoplasmic reticulum (ER), insulin signaling, and immune-related pathways. Among these, the most significant heat-stress-related pathway was protein processing in ER, indicating that this pathway is critical for the heat-stress response. After consistent heat stress at 29⯰C, the total antioxidant capacity (T-AOC), the activities of total superoxide dismutase (T-SOD) and catalase (CAT), and the mRNA expression of manganese SOD (Mn-SOD), CAT, and glutathione peroxidase 1 and 7 (GPx1 and GPx7) in the treated groups showed the same trend of first increasing and then decreasing. Levels of malondialdehyde (MDA) content did not show significant differences between samples at 0â¯h and 3â¯h, but significantly increased by 6â¯h, and thereafter decreased. The liver tissue was normal at 0â¯h (29⯰C); however, it suffered histological damage with increased duration of the heat stress. Above all, heat stress at 29⯰C seemed to cause oxidative damage and dysfunction in pikeperch liver between 3â¯h and 48â¯h. The present results indicate that pikeperch have the capacity to defend against heat stress and maintain relative balance of oxidation-reduction reactions mainly through activating the antioxidant system, protein processing in ER, the insulin-signaling pathway, and immune-related pathways.
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Resposta ao Choque Térmico , Fígado/metabolismo , Estresse Oxidativo , Percas/genética , Transcriptoma , Animais , Temperatura Alta , Fígado/imunologia , Oxirredução , Percas/imunologiaRESUMO
The pikeperch Sander lucioperca is an economically important freshwater species that is currently threatened by higher summer temperatures caused by global warming. To clarify the physiological state of pikeperch reared under relatively high temperatures and to acquire valuable biomarkers to monitor heat stress in this species, 100 fish were subjected to five different temperature treatments, ranging from 23⯰C (control) to 36⯰C. The physiological and biochemical indexes of liver and blood were determined, and heat-shock cognate 70â¯kDa protein (Hsc70) mRNA expression profiles were analyzed. The results showed that the activities of superoxide dismutase, catalase, and glutathione peroxidase in heat-stressed pikeperch first increased and then decreased, exhibiting peaks at 34⯰C, 28⯰C, and 28⯰C, respectively. The level of thiobarbituric acid-reactive substances (TBARS) in all experimental groups was significantly higher than that of the control. The numbers of red blood cells, the packed-cell volume, and the contents of hemoglobin were significantly higher in the 34⯰C and 36⯰C treatment groups. Under heat stress, the albumin, cholesterol, and triglycerides contents decreased with increasing temperatures. Real-time fluorescence-based quantitative RT-PCR showed that Hsc70 mRNA levels increased in all eight of the tested tissues under heat stress. Expression reached maximum levels at 34⯰C in the muscle, heart and gill tissues, and at 36⯰C in the other five tissues. These results demonstrate that several physiological and biochemical phenotypes, such as oxidative stress, antioxidant enzymes and molecular chaperones, could be important biomarkers of heat stress in pikeperch, and are potentially valuable to uncover the mechanisms of heat-stress responses in fish.
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Proteínas de Peixes/metabolismo , Proteínas de Choque Térmico HSC70/metabolismo , Resposta ao Choque Térmico , Percas/metabolismo , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Contagem de Eritrócitos , Proteínas de Peixes/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSC70/genética , Resposta ao Choque Térmico/genética , Hemoglobinas/análise , Fígado/enzimologia , Fígado/metabolismo , Estresse Oxidativo , Percas/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma that affects the brain, skin, and bone marrow. We describe the case of a 75-year-old man who was admitted to the hospital after 4â h of stomach aches. A thorough physical examination indicated stomach discomfort and skin discoloration. Laboratory tests revealed thrombocytopenia and elevated lactate dehydrogenase levels. A computed tomography scan of the abdomen revealed that the small intestine wall was thickened, edematous, and necrotic. The necrotic small bowel was surgically removed, revealing many little round, homogenous, and unusual cells in the mesenteric vein. In-situ hybridization revealed that these cells were positive for PAX5, CD20, CD79a, CD10, and BCL2, as well as Epstein-Barr virus-encoded small RNA. After 1 week of hospitalization without treatment, the patient was diagnosed with IVLBCL and died of multiple organ dysfunction syndrome. IVLBCL is a rare illness that affects the small intestine and possibly the gastrointestinal system. It has an insidious start, a fast development, and a dismal prognosis. Knowing its clinicopathologic traits helps in understanding the illness, making an early diagnosis, and preventing rapid worsening.
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Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Idoso , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Hibridização In Situ , Intestino Delgado/cirurgia , Intestino Delgado/patologiaRESUMO
Whether the optimization of fixed surface and sliding surface coupling mechanism is related to the hierarchical level of functionally graded porous stem is unknown. The functionally graded porous finite element stem models were constructed using tetrahedral microstructure with the porosities of 47-95%. The stress distribution for femoral bone gradually strengthened, the stress shielding was decreased along the increase of hierarchical levels of the stem after implantation. The coupling mechanism of fixed and sliding surfaces can be optimized by the functional gradient porous stem, the performance advantages become more prominent with the increase of hierarchical levels of the structure.
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Claudin-low breast cancer (CLBC) is a subgroup of breast cancer discovered at the molecular level in 2007. Claudin is one of the primary proteins that make up tight junctions, and it plays crucial roles in anti-inflammatory and antitumor responses as well as the maintenance of water and electrolyte balance. Decreased expression of claudin results in the disruption of tight junction structures and the activation of downstream signaling pathways, which can lead to tumor formation. The origin of Claudin-low breast cancer is still in dispute. Claudin-low breast cancer is characterized by low expression of Claudin3, 4, 7, E-cadherin, and HER2 and high expression of Vimentin, Snai 1/2, Twist 1/2, Zeb 1/2, and ALDH1, as well as stem cell characteristics. The clinical onset of claudin-low breast cancer is at menopause age, and its histological grade is higher. This subtype of breast cancer is more likely to spread to lymph nodes than other subtypes. Claudin-low breast cancer is frequently accompanied by increased invasiveness and a poor prognosis. According to a clinical retrospective analysis, claudin-low breast cancer can achieve low pathological complete remission. At present, although several therapeutic targets of claudin-low breast cancer have been identified, the effective treatment remains in basic research stages, and no animal studies or clinical trials have been designed. The origin, molecular biological characteristics, pathological characteristics, treatment, and prognosis of CLBC are extensively discussed in this article. This will contribute to a comprehensive understanding of CLBC and serve as the foundation for the individualization of breast cancer treatment.
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BACKGROUND: Low grade glioma is one of the most common lethal cancers in the human nervous system. Emerging evidence has demonstrated that homeobox A cluster (HOXA) gene family plays a critical role in the transcriptional regulation as well as cancer initiation and progression. However, the expression, biological functions and upstream regulatory mechanism of 11 HOXAs in low grade glioma are not yet clear. METHODS: In this study, we utilized various public databases and bioinformatics analyzed, including TCGA, CGGA, Rembrandt, HPA, LinkedOmics, cBioPortal, TISDIB, single-sample GSEA (ssGSEA), TIMER, LnCeVar, LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating, characteristic (ROC) analyses, GDSC and CTRP databases to analyzed the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, TMB, immune subtype, immune cell infiltration, immune modulator, ceRNA network and drug sensitivity of 11 HOXAs. Growth curve and transwell assays were utilized to study the biological characteristics of HOXA6 in LGG progression. RESULTS: In the present study, we found that 11 HOXAs (HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA3) were consistently up-regulated in LGG tissues and GBM tissues. Up-regulated of the HOXAs expression were significantly correlated with higher tumor stage, IDH mutation status, 1p/19q co-deletion, histological type and primary therapy outcome. Survival analyses showed that higher expression of HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 were correlated with shorter overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in LGG patients. Univariate and multivariate analyses revealed that HOXA1, HOXA6 expression and tumor grade, age, primary therapy outcome and age were independent factors affecting the prognosis of LGG patients. ROC curve analysis of HOXAs showed that HOXAs had a high accuracy (AUC > 0.80) in predicting LGG. Furthermore, gene functional enrichment analysis indicated that HOXAs mainly involved in the inflammatory response and immune regulation signaling pathway. CNV and DNA methylation significantly affect the expression of HOXAs. Finally, we uncover that HOXAs expression are highly correlated with immune cells infiltrate, immune modulator and drug sensitivity. We also uncover that the HOXAs related ceRNA network in LGG. More importantly, we found that HOXA6 was highly expressed in LGG cells lines and significantly affected their proliferation and migration abilities. CONCLUSIONS: In conclusion, our data demonstrated that HOXA was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LGG.
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Neoplasias Encefálicas , Genes Homeobox , Glioma , Proteínas de Homeodomínio , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Glioma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , HumanosRESUMO
Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of lung adenocarcinoma (LUAD). LncRNA-AP000695.2 (ENSG00000248538) is a long non-coding RNA (lncRNA) that is widely increased in many tumor types including lung adenocarcinoma (LUAD). However, the aberrant expression profile, clinical significance, and biological function of AP000695.2 in human lung adenocarcinoma (LUAD) need to be further investigated. This study mines key prognostic AP000695.2 and elucidates its potential role and molecular mechanism in regulating the proliferation and metastasis of LUAD. Here, we discovered that AP000695.2 was significantly upregulated in lung adenocarcinoma tissues compared with healthy adjacent lung tissue and higher in LUAD cell lines than in normal human bronchial epithelial cell lines. A higher expression of AP000695.2 was positively correlated with aggressive clinicopathological characteristics, and AP000695.2 served as an independent prognostic indicator for the overall survival, disease-free survival, and progression-free survival in patients with LUAD. Receiver operating curve (ROC) analysis revealed the significant diagnostic ability of AP000695.2 (AUC = 0.838). Our in vivo data confirmed that AP000695.2 promotes the proliferation, migration, and invasion of LUAD cells. GSEA results suggested that AP000695.2 co-expressed genes were mainly enriched in immune-related biological processes such as JAK-STAT signaling pathway and toll-like receptor signaling pathway. Single-sample GSEA analysis showed that AP000695.2 is correlated with tumor-infiltrating immune cells in lung adenocarcinoma. Our findings confirmed that AP000695.2 was involved in the progression of lung adenocarcinoma, providing a novel prognostic indicator and promising diagnostic biomarker in the future.
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BACKGROUND: Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression. METHODS: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too. RESULTS: We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells. CONCLUSION: YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.
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Neoplasias Encefálicas , Glioma , Humanos , Metilação de DNA , Proteínas de Checkpoint Imunológico , Variações do Número de Cópias de DNA , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glioma/patologia , Neoplasias Encefálicas/patologia , Prognóstico , Movimento Celular/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Extra spindle pole bodies-like 1 (ESPL1), a cysteine endopeptidase, plays a vital role in chromosome inheritance. However, the association of ESPL1 with prognosis and immune infiltration in lung adenocarcinoma (LUAD) has not yet been explored. Here, we analyzed the expression level, prognostic values, diagnostic value, and immune infiltration level in LUAD using various databases. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays were used to detect the expression of ESPL1 in LUAD tissues and cell lines. In this study, we found that ESPL1 was upregulated in LUAD and a higher expression of ESPL1 was correlated with unfavorable prognosis in LUAD. Meanwhile, Cox hazard regression analysis results suggested that ESPL1 may be an independent prognostic factor for LUAD. Moreover, we demonstrated that ESPL1 expression was significantly correlated with immune infiltration of Th2 and dendritic cells in LUAD. We also confirmed that DNA copy number amplification and DNA hypo-methylation were positively correlated with ESPL1 expression in LUAD. Additionally, DNA copy number amplification was significantly associated with adverse clinical outcomes in LUAD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) confirmed that ESPL1 was mainly involved in the DNA replication and glycolysis signaling pathway. Finally, we revealed that ESPL1 was highly expressed in LUAD tissues and cell lines. Knockdown of ESPL1 significantly inhibited cell migration and the invasion abilities of LUAD. Our study comprehensively confirmed that ESPL1 expression may serve as a novel prognostic biomarker for both the clinical outcome and immune cell infiltration in LUAD.
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We revealed that SNX20 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that SNX20 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on SNX20 to predict the 1-, 3-, or 5-year survival in LGG patients. Furthermore, we found that DNA hypomethylation results in its overexpression in LGG. In addition, functional annotation confirmed that SNX20 was mainly involved in the immune response and inflammatory response related signaling pathways, including the T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and the NF-kappa B signaling pathway. Finally, we determined that increased expression of SNX20 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG. Importantly, we found that SNX20 was highly expressed in glioma cell lines. Depletion of SNX20 significantly inhibits glioma cell proliferation and migration abilities. This is the first study to identify SNX20 as a new potential prognostic biomarker and characterize the functional roles of SNX20 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.
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Neoplasias Encefálicas , Glioma , Biomarcadores , Biomarcadores Tumorais , Metilação de DNA , Humanos , Isocitrato Desidrogenase/genética , Prognóstico , Nexinas de Classificação/genéticaRESUMO
INTRODUCTION: Viola betonicifolia is a rich source of numerous secondary metabolites, such as alkaloids, flavonoids, tannins, phenolic compounds, saponins, triterpenoids, and so on, that are biologically active towards different potential biomedical applications. To broaden the potential use of Viola betonicifolia in the realm of bionanotechnology, we investigated the plant's ability to synthesize gold nanoparticles (Au NPs) in a green and efficient manner for the very first time. METHODS: The gold nanoparticles (VB-Au NPs) were synthesized using the leaves extract of Viola betonicifolia, in which plant's secondary metabolites function as both reducing and capping agents. The VB-Au NPs were successfully characterized with spectroscopic techniques. The antimicrobial properties of the VB-Au NPs were further explored against bacterial and mycological species. Additionally, their antioxidant, cytotoxic, and cytobiocompatibility properties were examined in vitro against linoleic acid peroxidation, MCF-7 cancer cells, and human mesenchymal stem cells (hMSCs), respectively. RESULTS: Results demonstrated that VB-Au NPs presented excellent antibacterial, antifungal, and biofilm inhibition performance against all the tested microbial species compared to plant leaves extract and commercially purchased chemically synthesized gold NPs (CH-Au NPs). Moreover, they also exhibited significant antioxidant potential, comparable to the external standard. The VB-Au NPs displayed good cytobiocompatibility with hMSCs and demonstrated excellent cytotoxic potential against MCF-7 cancer cells compared to CH-Au NPs. The current work presents a green method for synthesizing VB-Au NPs with enhanced antioxidant, antimicrobial, cytotoxic and biofilm inhibition efficacy compared to CH-Au NPs might be attributed to the synergistic effect of the nanoparticle's physical properties and the adsorbed biologically active phytomolecules from the plant leaves extract on their surface. CONCLUSION: Thus, our study establishes a novel ecologically acceptable route for nanomaterials' fabrication with increased and/or extra medicinal functions derived from their herbal origins.
Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Viola , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Ouro , Química Verde , Humanos , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
As a kind of chronic inflammatory diseases, Rheumatoid arthritis (RA) has a low cure rate and easy recurrence. It has widely reported that abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways are associated with the development of RA inflammation. Blocking the inflammatory signaling pathways of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) can delay the development of RA. Ononin is a natural isoflavone glycoside and plays a key role in modulating inflammation related signaling pathways. However, whether Ononin exerts anti-inflammatory effects on RA inflammation remains unknown. In this study, we evaluated the therapeutic effect of Ononin on RA by establishing a tumor necrosis factor α (TNF-α)-induced RA-FLS cell model. Our data confirmed that Ononin could alleviate TNF-α-induced RA-FLS and MH7A cells viability, increase cell apoptosis, decrease the production of pro-inflammatory cytokines like interleukin-1ß (IL-1ß) and interleukin 6 (IL-6), and further inhibit the abnormal activation of NF-κB and MAPK pathways. Our results suggested that Ononin could be a potential therapeutic agent for RA.
Assuntos
Apoptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Glucosídeos/farmacologia , Isoflavonas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Sinoviócitos/metabolismo , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Fibroblastos/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Although excellent clinical outcomes of supercapsular percutaneously assisted total hip arthroplasty (SuperPath) have been reported, the peri-operative blood loss has rarely been reported. The current study determined the blood loss during SuperPath and compared the blood loss with conventional posterolateral total hip arthroplasty (PLTH). METHODS: This retrospective study enrolled patients who underwent unilateral primary THA between January 2017 and December 2019. The demographic data, diagnoses, affected side, radiographic findings, hemoglobin concentration, hematocrit, operative time, transfusion requirements, and intra-operative blood loss were recorded. The peri-operative blood loss was calculated using the OSTHEO formula. Blood loss on the 1st, 3rd, and 5th post-operative days was calculated. Hidden blood loss (HBL) was determined by subtracting the intra-operative blood loss from the total blood loss. RESULTS: Two hundred sixty-three patients were included in the study, 85 of whom were in the SuperPath group and 178 in the posterolateral total hip arthroplasty (PLTH) group. Patient demographics, diagnoses, affected side, operative times, and pre-operative hemoglobin concentrations did not differ significantly between the two groups (all P > 0.05). Compared to the PLTH group, the SuperPath group had less blood loss, including intra-operative blood loss, 1st, 3rd, and 5th post-operative days blood loss, and HBL (all P < 0.05). Total blood loss and HBL was 790.07 ± 233.37 and 560.67 ± 195.54 mL for the SuperPath group, respectively, and 1141.26 ± 482.52 and 783.45 ± 379.24 mL for the PLTH group. PLTH led to a greater reduction in the post-operative hematocrit than SuperPath (P < 0.001). A much lower transfusion rate (P = 0.028) and transfusion volume (P = 0.019) was also noted in the SuperPath group. CONCLUSION: SuperPath resulted in less perioperative blood loss and a lower transfusion rate than conventional PLTH.